DOI 10.1007/s00345-016-1899-y LETTER TO THE EDITOR Is there a role for extracorporeal shock wave therapy for erectile dysfunction unresponsive to phosphodiesterase type 5 inhibitors? Zi jun Zou 1 Zhi hong Liu 1 Liang you Tang 1 Yi ping Lu 1 Received: 1 May 2016 / Accepted: 13 July 2016 Springer-Verlag Berlin Heidelberg 2016 Dear Editor We read with great interest the invited review by Fojecki and colleagues regarding the role of extracorporeal shock wave therapy (ESWT) in urology [1]. The authors systematically reviewed randomized controlled trials (RCTs) published before November 9, 2015, to have examined ESWT in urologic diseases, including Peyronie s disease, chronic pelvic pain and erectile dysfunction (ED). In the article, they focused on the role of ESWT in patients with ED who had previously responded to a phosphodiesterase type 5 inhibitor (PDE5i). Those with ED unresponsive to PDE5is were not mentioned, likely due to lack of RCTs and the assumption that they probably also benefit from ESWT treatment. The first double-blind, sham-controlled study examining the role of ESWT for PDE5i non-responders was published at the end of 2015 [2] and reported that penile ESWT can convert a PDE5i non-responder to a responder. In terms of erection hardness score (EHS) and the erectile function (EF) domain of the International Index of Erectile Function (IIEF) score, positive outcomes were achieved in 54.1 and 40.5 % of participants 4 weeks, respectively, after completing 12 sessions of ESWT, while no improvement was observed in the sham-controlled group (p < 0.05). When the blinded segment of the protocol had been completed, a This comment refers to the article available at doi:10.1007/ s00345-016-1834-2. * Yi ping Lu yipinglu@163.com 1 Urological Institute, Urological Department, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu 610041, Sichuan, People s Republic of China proportion of patients in the sham control group underwent the same ESWT as those in the treatment group, and their ED also improved significantly. In that study, more than half non-responders were able to achieve an erection hard enough for vaginal penetration (EHS score = 3) with the aid of a PDE5i. Additionally, penile blood flow, measured using the flow-mediated dilation technique, was significantly ameliorated. In 2012, before the RCT, the same group from Israel had already published their clinical experiences of ESWT in patients poorly responsive to PDE5is, suggesting that it improved non-responders sensitivity to PDE5is and restored penile hemodynamic response to PDE5is [3]. Despite a lack of consistency in the methods of used, three other single-arm clinical trials reported promising outcomes of ESWT for PDE5i non-responders [4 6]. According to the current best evidence, the effect of ESWT on this type of ED could last for 4 months [5], and the modality also had the potential to restore spontaneous erection [5]. A summary of the current literature is shown in Table 1. To illuminate further the potential therapeutic benefits of ESWT on PDE5i non-responders, a large, multicenter, long-term follow-up RCT is still required. Additionally, robust patient selection strategies and the optimal study protocol need to be defined, and the underlying physiological mechanism of ESWT in ED requires exploration. Nonetheless, in our opinion the current evidence is sufficiently strong to recommend that patients with ED who do not respond adequately to oral PDE5i treatment should be treated with ESWT, before a trial of intracavernous vasoactive. It appears that ESWT is an effective noninvasive means of improving response to PDE5is and may lead to the recovery of spontaneous EF in some patients.
Table 1 Summary of current evidence for extracorporeal shock wave therapy in patients with erectile dysfunction poorly responsive to phosphodiesterase type 5 inhibitors Kitrey [2] RCT 37 (treated) versus 18 (controlled) Omnispec ED 1000 1500 pulses of Bechara [4] Single arm 20 Renova NR 5000 pulses of Chung [5] Single arm 30 Duolith SD1 ultra 3000 pulses of 0.25 mj/mm 2, 6 Hz Distal, mid and proximal penile shaft, and bilateral crura (300 on each location) Each corpus cavernosum (900), each crus (1600) Distal penis (1000), base of penis (1000), each crus (500) for 3 weeks, repeated after a 3-week interval 1 session/week for 4 weeks for 6 weeks Yes 1 month Effective rate: 54.1 % (ESWT) versus 0 % (sham) versus 56.3 % (active sham) in EHS; 40.5 % (ESWT) versus 0 % (sham) versus 25 % (active sham) in IIEF-EF; all p < 0.05 Yes 3 months 60 % of patients responded to ESWT assessed by IIEF-6, SEP2, SEP3 and GAQ No 6 weeks and 4 months 18 (60 %) patients increased 5 points in IIEF-5. Of these men, 15 could achieve spontaneous erections enough for penetration. Observed benefits persisted at 4 months Objective Significant improvement
Table 1 continued Ruffo [6] Single arm 31 Renova 3600 pulses of Each corpus cavernosum and crus (900) 1 session/week for 4 weeks No 1 and 3 months (1) IIEF-EF: 16.54 ± 6.35 versus 21.13 ± 6.31 21.03 ± 6.38 (3 months). (2) SEP2 (yes): 61 % versus 86 % 89 % (3 months). (3) SEP3 (yes): 32 % versus 58 % 62 % (3 months); all p < 0.05. (4) GAQ: at 1 month and 3 months, difference was not significant Objective
Table 1 continued Objective Gruenwald [3] Single arm 29 Omnispec ED 1000 300 pulses of ; overall 1500 pulses in a session Distal, mid and proximal penile shaft, and bilateral crura (300 on each location) for 3 weeks, repeated after a 3-week interval No use of PDE5i at first follow-up, use at the second 1 and 2 months (1) Mean IIEF- ED scores increased from 8.8 ± 1.0 to 12.3 ± 1.0 at FU1 (p = 0.035). At FU2, IIEF- ED increased to 18.8 ± 1.0 (p < 0.0001); (2) 72.4 % (p < 0.0001) reached an EHS of 3 by FU2 Significant improvement at 1 month RCT randomized controlled trial, ESWT extracorporeal shock wave therapy, EHS erection hardness score, IIEF-EF erectile function (EF) domain of the International Index of Erectile Function, IIEF-5 and IIEF-6 International Index of Erectile Function questions 5 and 6, SEP2 and SEP3 Sexual Encounter Profile questions 2 and 3, GAQ Global Assessment Question, not available, FU1 and FU2 first and second follow-up
Acknowledgments This work was supported by the Science and Technology Foundation of the Sichuan Province (2014JY0183 to Yiping Lu) and the Science and Technology Foundation of the Chengdu City (2014-HM01-00301-SF to Yi-ping Lu). Authors contribution ZJ Zou and YP Lu wrote and edited the manuscript. ZH Liu and LY Tang collected the data. Compliance with ethical standards Conflict of interest The authors declare that they have no conflict of interest. References 1. Fojecki GL, Tiessen S, Osther PJS (2016) Extracorporeal shock wave therapy (ESWT) in urology: a systematic review of outcome in Peyronie s disease, erectile dysfunction and chronic pelvic pain. World J Urol. doi:10.1007/s00345-016-1834-2 2. Kitrey ND, Gruenwald I, Appel B et al (2016) Penile low intensity shock wave treatment is able to shift PDE5i nonresponders to responders: a double-blind, sham controlled study. J Urol 195(5):1550 1555 3. Gruenwald I, Appel B, Vardi Y (2012) Low-Intensity extracorporeal shock wave therapy-a novel effective treatment for erectile dysfunction in severe ED patients who respond poorly to PDE5 inhibitor therapy. J Sex Med 9(1):259 264 4. Bechara A, Casabé A, De Bonis W, Nazar J (2015) Effectiveness of low-intensity extracorporeal shock wave therapy on patients with erectile dysfunction (ED) who have failed to respond to PDE5i therapy: a pilot study. Arch Esp Urol 68(2):152 160 5. Chung E, Cartmill R (2015) of clinical efficacy, safety and patient satisfaction rate after low-intensity extracorporeal shockwave therapy for the treatment of male erectile dysfunction: an Australian first open-label single-arm prospective clinical trial. BJU Int 115(suppl 5):46 49 6. Ruffo A, Capece M, Prezioso D et al (2015) Safety and efficacy of low intensity shockwave (LISW) treatment in patients with erectile dysfunction. Int Braz J Urol 41(5):967 974